Wednesday, May 13, 2009

If we listen to the leadership of the Obama healthcare reform effort, we cannot help but be impressed by the consistent focus on the development and utilization of innovative health technologies as a significant element in efforts to improve quality and control costs. The theme was reiterated on May 11 by Margaret Hamburg, FDA commissioner-designate, in a confirmation hearing (Video here) before the Senate Health, Education Labor and Pensions Committee. And the Congress - at least the majority - is on board as well; witness full HELP Committe hearings on innovative healthcare delivery systems scheduled for May 13 and 14 .

At the same time, recent Medicare program regulatory publications and coverage policy determinations can only cause us to question whether the commitment to innovation has as yet penetrated to the operational level. Last week, advocates of personalized medicine and genetic tesing were handed a setback as Medicare issued a Proposed Decision Memo for Pharmacogentic Testing for Warfarin Response. Warfarin is a commonly prescribed anticoagulant used to prevent blod clot formation in at risk patients; at any given time, millions of Americans are on Warfarin therapy. The potential vlue of pharmacogentic testing for Warfarin sensitivity is outlined in the NCA:

Warfarin has a narrow therapeutic window, meaning that there is a small difference in dosage (at times, less than one milligram of warfarin per day) between dosing that is too little, just right, or too much. Standard clinical practice for warfarin titration requires periodic testing of its anticoagulant effect. This is assessed with the prothrombin time (PT) and the International Normalized Ratio (INR). In the PT/INR test, the ratio of the patient's PT to the mean PT for a group of normal individuals is calculated, and that ratio is then raised to a power which adjusts for differences among different types of reagents used in the test procedure. Commonly, the PT/INR is assessed frequently during the first few weeks or months while warfarin therapy is begun, and after that, less frequently when the patient demonstrates a stable response. More frequent testing may be required if the patient exhibits signs of over- or under-treatment or if the patient begins (or stops) taking another drug that is recognized to affect warfarin action or metabolism.

The putative use of pharmacogenomic testing is to predict a patient’s response to warfarin before the initiation of the drug. This would be an once-in-a-lifetime test, absent any reason to believe that the patient’s personal genetic characteristics would change over time.

The Warfarin test had been seen as a major step forward for genetic testing bcause of the size of the potential affected population and the therapeutic utility of the test - more accurate prediction of patient-specific Warfarin response wold, it was argued, hlp to reduce adverse events associated with over-dosing and/or under-dosing during early stages of the dose titration process. But Medicare's NCA concluded that "CMS believes that the available evidence does not demonstrate that pharmacogenomic testing to predict warfarin responsiveness improves health outcomes in Medicare beneficiaries", and proposed that "."Pharmacogenomic testing to predict warfarin responsiveness is covered only when provided to Medicare beneficiaries who are candidates for anticoagulation therapy with warfarin and only then in the context of a prospective, randomized, controlled clinical study when that study meets [specific detailed] standards." Coverage with Evidence Development (CED) - viewed by some as an entry wedge for promising but as yet unproven technologies, by others as one more way for Medicare to temporize in accepting innovations.

This week, the imaging community received a similar jolt, as CMS published its Decision Memo for Screening Computed Tomography Colonography (CTC) for Colorectal Cancer affirming a proposed non-coverage determination originally released in February. CTC advocates point to the sensitivity of the test, its lower cost, and its greater acceptability to the patient population as compared to colonoscopy. Research indicates that many individuals who ought to be screened are unwilling to undergo the colonoscopy procedure; CTC would increase the proportion of at-risk individuals screened, thereby identifying and allowing early treatment of more colorectal cancers; while CTC requires a confirmatory colonoscopy for "positives", advocates claim the total cost impact of using the new technology for initial screenings would also be beneficial.

During the formal 30 day comment period following that release, CMS had met (on March 3) with representatives of the American Cancer Society, the American College of Radiology, and the American Gastroenterological Association, as well as (on March 10) with representatives of the Medical Imaging and Technology Alliance; the Agency also received 357 written comments on the proposed non-coverage decision. Industry representatives and the supportive medical societies had been hopeful that their meetings and comments, along with new clinical data provided during the comment period, would change CMS' proposed policy.

A review of the formal comments is instructive. First. they were overwhelmingly in favor of coverage for CTC - "Of the total 357 comments, 16 expressed agreement with the proposed decision not to expand the colorectal cancer screening benefit to include coverage of the CT colonography screening test, and 337 commenters were opposed to it. Of the 357 total commenters, 101 were one of a couple of variations of form letters. Four commenters did not offer a specific opinion on whether on not the test should be covered for average risk individuals". CMS tends to discount the form letters, as they are generated by highly-interested third parties (usually the affected technology companies), but they do in fact provide a sense of the depth of spport from the general user communty.

Among organizations submitting comment, 6 favored coverage for CTC and 4 supported CMS' proposed noncoverage policy. CTC supporters were the American Cancer Society, medical societies the American College of Radiology (combined comments with the Society of Gastrointestinal Radiology and the Society of Computed Tomography and Magnetic Resonance) and the American Gastroenterological Association, device industry trade associations the Advanced Medical Technology Association (AdvaMED) and the Medical Imaging and Technology Alliance, and private insurer United Health Care. Those opposed were the American College of Gastroenterology (ACG), the American College of Preventive Medicine (ACPM), the American Society for Gastrointestinal Endoscopy, and insurance industry trade association American’s Health Insurance Plans (AHIP). A pattern is discernible: organizations that "win" if CTC is covered are favorable to the technology (CT companies, imaging organizations, radiologists); "losers" (gastroenterologists, many insurers) are opposed to coverage. There is also room for simpler disagreement (e.g. American Cancer Society, American College of Preventive Medicine).

It is tempting to view these coverage policy developments as institutional efforts by CMS to avoid incurring the costs asociated with new technologies. But a careful reading of the documents - which in both cases are lengthy, highly detailed, and heavily documented - leads to a more complex and less emotionally satisfying understanding. For warfarin testing, CMS essentially concludes that, whatever the accuracy of pharmacogenetic testing for dosage titration, the practical protocols for use of the test are not yet established and/or documented in a manner that provides clearevidence of superiority in clinical practice; more needs to be known about how to use the test before it can be seen as superior to current titration protocols; ergo CED:

A clinical study seeking Medicare payment for pharmacogenomic testing to predict warfarin responsiveness provided to the beneficiary pursuant to Coverage with Evidence Development (CED) must address one or more aspects of the following question.

Prospectively, in Medicare aged subjects whose warfarin therapy management includes pharmacogenomic testing to predict warfarin response, what is the frequency and severity of the following outcomes, compared to subjects whose warfarin therapy management does not include pharmacogenomic testing?

Major hemorrhage

Minor hemorrhage

Thromboembolism related to the primary indication for anticoagulation

Other thromboembolic event

Mortality

Answer those questions in clinical practice for the Medicare population, the challenge is made, and then come back for broad coverage outside the research setting.

For CTC, CMS concludes that none of the published research on CTC effectiveness allows conclusions to be drawn about the utility of the test in the Medicare (> age 65) population, and that population differs in meanigful ways from the populations repoted in published research:

Overall, when considering potential benefits and potential harms, there is insufficient evidence to conclude that the use of CT colonography improves health outcomes in Medicare beneficiaries. Data on the health outcomes, potential benefits and harms from small lesions, extracolonic findings and radiation are needed from well designed clinical studies. In addition, with the higher prevalence of polyps in the older Medicare population, the rate of referral to optical colonoscopy is extremely important and also unknown at this point. If there is a relatively high referral rate, the utility of an intermediate test such as CT colonography is limited.

Medicare is consistent. Innovative technologies must be shown to be relevent to the Medicare population, and they must be shown to bepractically useful in the clinical setting. The lesson is clear: bringing innovative technologies into standard use is a more complex challenge than is sometimes assumed by developrs.

About Me

A senior healthcare executive with special insight into the impact of public policy on business planning and operations, Ed Berger founded Larchmont Strategic Advisors in 2005 to help life sciences companies deal effectively with the challenges and opportunities posed by the coverage and reimbursement requirements of public and private payers and a rapidly evolving healthcare regulatory and policy environment.